Inhibition of carbohydrate oxidation during the first minute of reperfusion after brief ischemia: NMR detection of hyperpolarized 13CO2 and H13CO3-.
Isolated rat hearts were studied by (31)P NMR and (13)C NMR. Hyperpolarized [1-(13)C]pyruvate was supplied to control normoxic hearts and production of [1-(13)C]lactate, [1-(13)C]alanine, (13)CO(2) and H(13)CO(-) (3) was monitored with 1-s temporal resolution. Hearts were also subjected to 10 min of global ischemia followed by reperfusion. Developed pressure, heart rate, oxygen consumption, [ATP], [phosphocreatine], and pH recovered within 3 min after the ischemic period. During the first 90 s of reperfusion, [1-(13)C]alanine and [1-(13)C]lactate appeared rapidly, demonstrating metabolism of pyruvate through two enzymes largely confined to the cytosol, alanine aminotransferase, and lactate dehydrogenase. (13)CO(2) and H(13)CO(-) (3) were not detected. Late after ischemia and reperfusion, the products of pyruvate dehydrogenase, (13)CO(2) and H(13)CO(-) (3) were easily detected. Using this multinuclear NMR approach, we established that during the first 90 s of reperfusion PDH flux is essentially zero and recovers within 20 min in reversibly-injured myocardium.
Merritt
Matthew E
ME
Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA. matthew.merritt@utsouthwestern.edu
Harrison
Crystal
C
Storey
Charles
C
Sherry
A Dean
AD
Malloy
Craig R
CR
D000818:Animals; D050260:Carbohydrate Metabolism; D002245:Carbon Dioxide / Q000032:analysis*; D002247:Carbon Isotopes / Q000032:analysis; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002247:Carbon Isotopes; D002245:Carbon Dioxide; D010100:Oxygen